Intermediates useful in the production of pesticides

ABSTRACT

A process for the production of a boronic acid of formula III, ##STR1## in which an organometallic of formula IV, ##STR2## in which formula IV, M represents a metallic moiety such as --MgX, X being a halogen or an alkali metal is treated with a trialkoxy borane of formula B(OR) 3 , R representing an alkyl group and the product is hydrolysed.

CROSS-REFERENCE

This is a division of Ser. No. 428,193 filed Oct. 27, 1989, now U.S.Pat. No. 5,068,403 which is a continuation of Ser. No. 025,230, filedMar. 12, 1987, now abandoned.

This invention relates to production of intermediates useful in themanufacture of pesticides.

In International Patent Application No. GB 85/00146 there are disclosedmethods for the preparation of compounds of formula I

    R.sub.A CR.sub.3 ═CR.sub.4 CHDR.sub.B                  I

in which formula:

R_(A) represents a group ArCR₁ R₂ --in which Ar represents a phenyl ornaphthyl group optionally substituted by one or more halogen, alkoxy,haloalkoxy, methylenedioxy, C₁ -C₆ alkyl or haloalkyl groups;

R₁ and R₂ together with the carbon to which they are attached representa C₃ -C₆ cycloalkyl group optionally substituted by one or more halogenatoms or C₁ -C₆ alkyl groups.

R₃ and R₄ which may be identical or differ, represent hydrogen, halogenor C₁ -C₆ alkyl groups and

R_(B) represents the residue of an alcohol R_(B) CHDOH in which D ishydrogen or cyano and of which the [IR,cis]2,2-dimethyl-3-(2,2-dibromovinyl) cyclopropane carboxylic ester issignificantly insecticidal,

the configuration of R_(A) and CHDR_(B) about the double bond beingmutually trans.

Compounds I in which R_(B) represents 4-fluoro-3-phenoxyphenyl are ofparticular interest and may be prepared inter alia by reaction of theGrignard reagent, 4-fluoro-3-phenoxyphenyl magnesium bromide with asuitable substrate. The bromide required for preparation of thisGrignard reagent (5-bromo-2-fluorodiphenyl ether) (II), has, however,been available hitherto only with difficulty. ##STR3##

It has now however been found that the bromide and other intermediatescan be generated in good yield from 2,4-dibromofluorobenzene, which isavailable commercially although generally contaminated with the isomer3,4-dibromofluorobenzene.

Accordingly, the present invention comprises a process for theproduction of a boronic acid of formula III, ##STR4## convertible into5-bromo-2-fluorodiphenyl ether (II), in which an organometallic offormula IV, obtainable from 2,4-dibromofluorobenzene, ##STR5## in whichformula IV M represents a metallic moiety such as --MgX, (X being ahalogen) or an alkali metal such as lithium is treated with a trialkoxyborane of formula B(OR)₃, R representing an alkyl group (e.g. a C₁ -C₆alkyl group which is preferably methyl) and the product is hydrolysed.

It has been found that the boronic acid III crystallizes readily andthat the crystals are substantially free of impurities and particularlyisomers of the acid III derived from metallation at the 4-bromo positionof 2,4-dibromofluorobenzene or derived from 3,4-dibromofluorobenzeneimpurity in the starting material.

Accordingly, in a preferred embodiment of the present process, theboronic acid III is crystallised and the crystals are isolated prior tofurther treatment.

The amount of the metal or metal alkyl used to treat2,4-dibromofluorobenzene and thus produce the organometallic IV may bereduced to 80% or less of the stoichiometric amount. Under theseconditions bromine at the 2-position in 2,4-dibromofluorobenzene mayreact in preference to bromine at the 4-position and2,4-dibromofluorobenzene may react in preference to3,4-dibromofluorobenzene present as a contaminant, so that a good yieldof the desired isomer of formula IV is obtained. Amounts less than 60%of stoichiometric are undesirable as the yield is unnecessarilydecreased.

The boronic acid III may be converted into the intermediate5-bromo-2-fluorodiphenyl ether II, by oxidation, suitably using hydrogenperoxide, to the corresponding phenol V the corresponding alkali metalphenoxide of which VI reacts with a halobenzene, in which the halogen ischlorine, bromine or iodine, under Ullman conditions e.g. in thepresence of a copper catalyst such as copper bronze or a Cu^(I) orCu^(II) halide to give II ##STR6##

The present invention includes in a further aspect an organometallic offormula IV, a boronic acid III, a phenol V, a phenoxide VI and processesas hereinbefore described for the conversion of 2,4-dibromofluorobenzeneto the organometallic IV, of the boronic acid III to the phenol V, ofthe phenol V to the phenoxide VI and of the phenoxide VI to theintermediate 5-bromo-2-fluorodiphenyl ether.

The invention is illustrated by the following Example:

Dihydroxy-(5-bromo-2-fluorophenyl)-borane

A solution of 2,4-dibromofluorobenzene (12.7 g, containing 30%3,4-dibromofluorobenzene) in dry tetrahydrofuran (THF) (10 ml) is addedover 5 min to a stirred suspension of magnesium turnings (1.15 g) in dryTHF (50 ml) under an atmosphere of nitrogen and cooled in a water bath.After 1 hour, when all the magnesium has reacted, this reagent is addedover 20 min to a stirred solution of trimethoxyborane (7 ml) in drydiethyl ether (80 ml) under an atmosphere of nitrogen and cooled at -78°C. The mixture is stirred at -78° C. for a further 15 min. and glacialacetic acid (6 ml) added followed by water (50 ml). The mixture iswarmed to room temperature, extracted with diethyl ether (×3), washedwith water, dried and the solvent evaporated under reduced pressure. Theresidue is stirred with carbon tetrachloride (30 ml) and then cooled at0° C. The crystals of dihydroxy-(5-bromo-2-fluorophenyl)-borane arefiltered off and washed with a little carbon tetrachloride. Yield 2.8 gm.p.t. 173°-174° C.

5-Bromo-2-fluorophenol

To a stirred solution of dihydroxy-(5-bromo-2-fluorophenyl)borane (2 g)in diethyl ether (10 ml) is added chloroform (10 ml) and 30% hydrogenperoxide (10 ml). The mixture is stirred for 18 hours at roomtemperature, diluted with water, extracted with diethyl ether (×3) andback extracted with 2M NaOH (or, in an alternative embodiment producingrelatively increased yields, with stronger sodium hydroxide, e.g. 5MNaOH). The aqueous layer is acidified with aqueous 2N HCI extracted withdiethyl ether (×3), dried and the solvent evaporated to give5-bromo-2-fluorophenol, yield 1.25 g. A sample is purified by t.l.c. onsilica gel eluted with 30% diethyl ether in petroleum ether b.p. 60°-80°C. n_(D) 1.5564. Alternatively, the product is distilled b.p.52°-54°/0.2 mm Hg.

5-Bromo-2-fluoro-diphenyl ether

Sodium hydride (0.2 g of 60% dispersion in oil) is added in smallportions to a stirred solution of 5-bromo-2-fluorophenol (1 g) in2-methoxyethyl ether (1 ml) under nitrogen and cooled in a water bath.Cuprous bromide (0.09 g) and a solution of bromobenzene (1.5 ml) in2-methoxymethyl ether (2 ml) were added and the mixture refluxed for 6hours. The mixture was poured onto water, extracted with petroleum etherb.p. 60°-80° (×3), washed with water, dried, solvent evaporated and theresidue distilled at 0.02 mm Hg b.pt. 80°-82° C. n_(D) 1.5708, Yield0.55 g.

We claim:
 1. A process for the production of 5-bromo-2-fluorodiphenylether, comprising oxidizing a boronic acid of formula III ##STR7## to5-bromo-2-fluorophenol, forming the alkali metal phenoxide of said5-bromo-2-fluorophenol and reacting the alkali metal phenoxide with ahalobenzene under Ullmann conditions.